Influence of Low Density Lipoprotein from Insulin-Dependent Diabetic Patients on Platelet Functions

Abstract

In the present work we studied in vitro the action of low density lipoproteins (LDL) isolated from normolipemic insulin-dependent diabetic (IDDM) patients on transmembrane cation transport, nitric oxide synthase (NOS) activity, and aggregating response to stimuli of platelets from healthy subjects to elucidate whether the modified interaction between circulating lipoproteins and cells might be one of the pathogenetic mechanisms of the increased platelet activation in IDDM. LDL were obtained by discontinuous gradient ultracentrifugation from 15 IDDM out-patients and 15 sex- and age-matched healthy subjects and used for incubation experiments with control platelets. Lipid composition and hydroperoxide concentrations were studied in LDL. Platelet aggregation responses to ADP, NOS activity, cytosolic Ca2+ concentrations, and platelet membrane Na+/K+-adenosine triphosphatase (Na+/K+-ATPase) and Ca2+-ATPase activities were measured after incubation. IDDM LDL showed an increased lysophosphatidylcholine content compared with that of control LDL. IDDM LDL significantly increased the platelet aggregating response to ADP, cytosolic Ca2+ concentrations, and plasma membrane Ca2+-ATPase activity and significantly reduced NOS activity and platelet membrane Na+/K+-ATPase activity compared with those of platelets incubated in buffer or cells incubated with control LDL. The effects exerted by IDDM LDL on platelet suspensions from healthy subjects mimic the alterations observed in platelets from diabetic subjects in basal conditions. Both the decreased activity of NOS and the higher cytoplasmic concentrations of Ca2+ might cause increased platelet activation, as observed in IDDM. In conclusion, the present study suggests a new mechanism with a potential role in the early development of atherosclerosis in diabetic patients, i.e. an altered interaction between circulating lipoproteins and platelets.

Chemical‐physical properties of lipoproteins in anorexia nervosa

“…increased fluidity of the membrane. This phenomenon can result either from increased phospholipids or increased unsaturated fatty acid content [21,22].…”

Platelet Interaction with Bioactive Lipids Formed by Mild Oxidation of Low-Density Lipoprotein

“…The mean values of LPC range between 2 and 5% LPC of total LDL phospholipids in most of the recent studies [65,66] (Corrinth and Siess, unpublished observations). LPC increases 2-10-fold dependent on the degree of LDL oxidation.…”

“…In a recent study, however, it has been observed that LDL isolated from insulin-dependent diabetic patients had a significant higher LPC content (9.62 8 2.04% of LDL phospholipids) as compared to LDL of healthy controls (4.55 8 1.86% of LDL phospholipids). The LDL of diabetic patients increased cytosolic Ca 2+ concentrations and potentiated ADP-induced aggregation [65] . Whether this effect was due to the increased LPC content of LDL of diabetic patients or other mechanisms, remains an open question.…”

Effects of taurine on plasma and liver lipids, erythrocyte ouabain sensitive Na efflux and platelet aggregation in Sprague Dawley rats

“…Stimulation of PAF receptor decreased Na-K ATPase in rat proximal tubule contributing to natriuresis (Handa et al, 2003). In in vitro study of platelet incubated with LDL, IDDM LDL significantly increased platelet aggregation and significantly reduced platelet membrane Na-K ATPase compared with control LDL (Rabini et al, 1999). …”

“…Na-K ATPase acts on Na reabsorption in distal tubule and collecting duct of kidney cell. Na-K ATPase is reduced in patients with insulin resistant diabetes, obesity and hypertension (Hakam et al, 2006; Rabini et al, 1999). Angiotensin receptor agonists inhibit proximal tubule Na-K ATPase in obese hypertensive rat and Na induced hypertension was accelerated with taurine deficiency (Hakam et al, 2006).…”